Our research program is concerned with developing and testing models of how cognitive processes are mediated in the human brain. This is accomplished via studies of patients with brain injury and disease, and via studies of normal individuals using functional brain imaging modalities. Our studies of semantic memory in patients with Alzheimer's disease (AD_) suggest that posterior cortical pathology results in a selective degradation of previously acquired knowledge. These degraded knowledge representations are, in turn, proposed to be responsible for work-finding problems, and to substantially contribute to poor memory in patients with A.D. Functional brain imaging studies of normal individuals using positron emission tomography have begun to elucidate the neural systems that mediate this knowledge . These studies indicate that knowledge about objects is represented by a distributed network of discrete cortical regions in which the attributes that define an object are stored adjacent to the brain areas that mediate perception of those attributes. In addition, using magnetic resonance imaging, we have obtained evidence that priming, a form of implicit learning that is preserved in patients with amnesia and in patients with AD, is mediated by decreased neural activity in specific brain regions. We have also used priming to evaluate memory and learning in normal elderly subjects. Although an age-related deficit int he ability to monitor how often an event has occurred has been previously documented, our studies show that this ability is intact when tested with implicit measures, thus indicating a problem gaining access to frequency information, rather than a problem in acquiring this information. Our studies of individuals infected with the Human Immunodeficiency Virus (HIV) have continued to document subtle cognitive dysfunction, and a relationship between this dysfunction and concentrations in cerebrospinal fluid of a potent neurotoxin, quinolinic acid, and with MRI abnormalities. Finally, studies of patients with Obsessive-Compulsive Disorder suggest that these patients may be overly attentive to certain aspects of the environment, which, in turn may interfere with information processing.